Development of Matrix Patches for Transdermal Delivery of a Highly Lipophilic Antiestrogen

• Published in: Drug development and industrial pharmacy 2003-01, Vol.29 (7), p.785-793
• Main Authors: Funke, Adrian Peter, Günther, Clemens, Müller, Rainer Helmut, Lipp, Ralph
• Format: Article
• Language: English
• Subjects: Adhesives - therapeutic use; Administration, Cutaneous; Animals; Antiestrogen; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Estrogen Receptor Modulators - pharmacokinetics; General pharmacology; Highly lipophilic drug; In Vitro Techniques; Lauric acid; Male; Medical sciences; Mice; Mice, Hairless; Permeability - drug effects; Permeation enhancers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Propylene glycol; Propylene Glycol - pharmacokinetics; Skin - metabolism; Skin Absorption - drug effects; Solubility; Technology, Pharmaceutical - methods; Time Factors; Transdermal drug delivery systems (TDSs)
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1081/DDC-120021778

Abstract The aim of this study was to develop matrix-type transdermal systems (TDSs) containing the highly lipophilic (log P = 5.82) antiestrogen (AE) and the permeation enhancers propylene glycol and lauric acid. For that purpose, permeation of AE from various adhesive matrices through excised skin of hairless mice was evaluated. It was found that pretreatment of the skin with permeation enhancers raised the transdermal flux of subsequently applied antiestrogen. Highest steady-state transdermal fluxes (1.1 µg cm−2 h−1) were obtained from Gelva®, polyacrylate adhesive, followed by 0.55 µg cm−2 h−1 from Oppanol® polyisobutylene, 0.31 µg cm−2 h−1 from BIO-PSA® silicone, and 0.12 µg cm−2 h−1 from Sekisui polyacrylate matrices. In order to develop TDS with high content of fluid permeation enhancer propylene glycol, two different strategies were investigated. One strategy was the addition of hydroxypropyl cellulose (HPC) as thickening agent to Gelva matrices. This allowed for propylene glycol loading levels of up to 30%, resulting in transdermal AE fluxes of 0.09 µg cm−2 h−1. On the other hand, a fleece-laminated backing foil was loaded with the described permeation enhancer formulation and laminated with polyacrylate adhesive layer, resulting in transdermal AE fluxes of 0.06 µg cm−2 h−1. However, application of these TDSs on skin pretreated with permeation enhancers raised the fluxes to 2.6 µg cm−2 h−1 from Gelva HPC and 0.46 µg cm−2 h−1 from fleece Sekisui.